The End of Methotrexate for Me

When first diagnosed with RA over five years ago, I was prescribed oral methotrexate (MTX). After a month of taking the pills, I felt terrible and was basically non-functional. It felt like a truck ran over me as I had no energy, felt sick at my stomach non-stop, and had headaches. The RA symptoms were bad enough but this just added insult to injury. My rheumatologist finally told me that I clearly could not tolerate the drug and to stop taking it. The side effects subsided within a few weeks.

Several years later, and with a different rheumatologist, I asked about taking MTX injections because I was desperately trying to find a treatment combination that worked. It was recommended to add MTX with the biological medicines I was taking as the combination of the two typically produces better results. I started take methotrexate via weekly self-injection and found that the nausea side effects were much less than with oral pills. I seemed to tolerate the MTX much better when injecting it and adding both folic acid and leucovorin. I rarely felt nausea and did not loose any hair.

But an increase in migraine headaches over the past year coincided with the time I started taking MTX. While not one of the more commonly reported side effects like nausea or hair loss, headaches can come from taking MTX.[i][ii] As my neurologist stated, the causes of the migraines are likely based on multiple factors including genetics, my fight with RA, and the medicines I take. During the past few months when the headaches increased in number, I completely stopped taking methotrexate in an effort to eliminate any possible triggers. We’ve been able to reduce the number of migraines through the use of gabapentin, a drug used for neuropathic pain, and botox injections (no, I don’t look any younger!). My rheumatologist suggested that I start retaking methotrexate by beginning with low doses initially and then increase back up to the dose I was taking before. I waited until I had been headache free for two weeks and then injected MTX. Within 48 hours I began to get migraines and fought off four bad headaches over the next five days. While it’s hard to determine direct cause and effect, this was enough for me to wonder if MTX was indeed a migraine trigger. I did not inject MTX the next week and did not have any bad migraines. I contacted my rheumy and she suggested I just stop MTX altogether. The good news is that during this time, Rituxan infusions that I started last September were starting to work at controlling my RA and this was during the time I had stopped taking MTX.

So for the time being, I’ll just stick with Rituxan as my main RA treatment. And I’ll be sitting in the infusion center this Wednesday starting my second series of doses.

23 Responses

this is interesting because I was taking gabapentin before I started mtx and perhaps this why I have not had terrible side effects. However, I have had the headache to occur. One thing I am trying to differentiate is the difference between fatigue and feeling lousy. I know that sounds strange.

Actually sounds like the best roads go for you. If I may suggest one thing? Stopping methotrexate cold turkey can cause bad flares (I know from first-hand experience). They generally suggest tapering it.

I took MTX for 8 years in various amounts. I thought I wasn’t having any side effects. No mouth sores, nausea, etc. I did lose hair, but it is common for women in my family to get thin hair as they age. One thing I noticed was that every time they increased my dosage my nodules got bigger. 3 different rheumy docs and each one always tried bumping me up to 6 tablets a week. We always had to back off that dosage for some reason or other. One nodule on my right index finger got so big that it squeezed the nerve and caused the tip of my finger to be numb all the time. So she took me off the MTX. Within 2 months all nodules went away. Totally! She said, “Well it is suspected that MTX can cause the nodules and increase them.” I don’t think they should just “suspect” anymore! I switched over to imuran to go along with the humira. Working pretty well!

I’m glad the Rituxan is beginning to work, Andrew! You’ve had a long, hard slog trying to find something that works for you. And I’m glad you’ve (probably) found and eliminated one of the migraine triggers. What a relief! Hang in there!

i have been having bad headaches and migraines for the past few years, maybe six or seven years. i’ve noticed that i’ve recently had a constant headache, sometimes bordering on the migraine pain i used to have. i’ve been on methotrexate since september ’13 and am wondering if that could be causing the headaches. i don’t think i have really seen any improvement in my symptoms either – with the methotrexate or the enbrel. glad you found what was leading to your migraines!

Interesting post. I’ve tended to get minor headaches from MTX, less with the injections then the pills. My biggest issue was nausea and generally feeling like crap the day after (the MTX hangover). I now take an anti-nausea med with MTX. However, that gives me wicked mind crushing headaches. So now, I take the MTX, the anti-nausea med, as much water as I can drink, a dose of Excedrin at bedtime, and then another dose of Excedrin when I first wake up. That keeps the headache to minor and the hangover away. The irony of the regiment however is comical.

I am glad the Rituxan is working for you and your headaches are less. It is really lousy to deal with pain on multiple fronts at once.

I couldn’t tolerate oral MTX either. Like many patients, it was the first drug that I was prescribed when I was diagnosed. As I’ve worked my way through the various biologics I have generally toyed with the idea of adding injectable MTX because I’ve heard that the side effects weren’t quite so bad. For you, things seem to have worked well so far. Your infusion therapy seems to be bringing you relief and you’ve found (and eliminated) a major trigger of your headaches. Hopefully this is the first steps to remission. Sending a smile and hug your way.

MTX has been used for RA treatment for a long time ago .It’s very efficient for almost population even having some side-effects.
I had used over 15 years, it controlled RA so well for me , but for a such long period, i had some S/E and tolerance. So i’ve stopped it and taken TNF until now, but about 60% to control my RA
I ‘m so happy and thank God for your finding of Rituxan as a efficient treatment for your RA at the moment

For me it took a long time…like 4 months. It tends to take longer than the TNF blockers because it only affects a certain phase of B cell production and it takes a long time for the cycle. Hang in there. I was about to give up, my rheumy kept saying it takes time, and then it finally kicked in. Hope it works for you!

Your MTX experience is very similar to mine.
I always have had a problem with migraines, but they went crazy on me when I was on mtx. I had so many, I was put on topamax to help. I switched to injections which did help the gastric effects, also unreal. topamax was HORRIBLE & might as well be called dope-amax.

I barely functioned. Still the rheumy wouldn’t change my drugs. I finally fired her, got the best rheumy ever now! Rituxin slams me, but only for a short time. I couldn’t tolerate the steroid pre injection, or the alternative.

I came on today after having infusion yesterday & jaw pain last night. Slightly better today.I wondered if anyone else had similar issues with jaw, also swollen nodes in neck and tender. I am always nervous to find out if anyone else has such things – is it bad, normal or whatever?

I also take azathioprine daily, in conjunction with my rituxin. No more mtx & I couldn’t handle laflunamide either, but that’s a whole story in itself!

Your story does sound similar to mine. I just had a Rituxan infusion today. My jaw always bothers me. I’ve tried everything. At my recent neck surgery, the anesthesiologist as me to open my mouth to see if I could open big enough for the tubes. He said that many with RA have jaw problems. I’ve also had tender and swollen lymph nodes in my neck and chest mostly when I was on other biologic medicines. My rheumy says it’s normal with RA since our immune system is out of whack. It could also be an infection so keep an eye on that. It the nodes keep bothering you, get them checked out by a hematologist. I had mine imaged and a bunch of blood tests run and everything was fine.

TMJ is relatively common with RA. Problem is that no doctor wants to touch it as there are no officially accepted treatment plan. I use a special nightguard, have tried muscle relaxants, and have botox injections into the associated muscles when being treated for migraines.

Andrew, I am fortunate not to be on any DMARDS yet, but I can totally sympathize with your dilemma. Ever since my RA diagnosis, I’ve seen a resurgence of my migraines, with yesterday being the worst I’ve had in many years. I’ve noticed a correlation between my fatigue and joint stiffness with the headaches. Whatever the case, I’m with you in that migraines are so incapacitating versus the pain in my hands and feet. I wouldn’t take an RA drug that caused them either! Glad you’re feeling better now. Thanks for sharing!!